Figure 1

The monocyte/phagocyte system. Two populations of bone-marrow derived monocytes, Ly6C^hi and Ly6C^lo monocytes enter the circulation. Ly6C^lo monocytes are primarily responsible for patrolling the vasculature, regulating neovascularization and monitoring endothelial cell homeostasis. Ly6^hi monocytes enter the tissues as part of their intrinsic function or in response to pro-inflammatory chemokines released at sites of injury by resident tissue macrophages. Upon entering the tissue, these monocytes can differentiate into macrophages in response to various inflammatory and immune stimuli specific to the tissue microenvironment. The phenotype of the differentiated infiltrating macrophages can be broadly classified as classically activated inflammatory (M1) or alternatively activated tissue remodeling/profibrotic (M2) macrophage populations. Resident tissue macrophages that originated from embryonic yolk sac and migrated to organs during development can be replenished either by proliferation of the resident population or by infiltrating differentiated macrophages that have survived following inflammation resolution. Solid arrows indicate major differentiation/activation pathways. Dotted arrows indicate secondary or minor differentiation pathways. CCL1, C-C chemokine ligand 1; CCR1, C-C chemokine receptor 1; CCR2, C-C chemokine receptor 2; CCR5, C-C chemokine receptor 5; CX ₃ CL1, C-X₃-C chemokine ligand 1; CX ₃ CR1, C-X₃-C chemokine receptor 1; GC glucocorticoid; IFN-γ, Interferon-γ; IL-4, Interleukin-4; IL-10, Interleukin-10; IL-13, Interleukin-13; TGF-β, Transforming Growth Factor β.